The effects of thiamine deficiency are being studied on the synthesis of acetylcholine and on the levels of cyclic AMP and cyclic GMP in rat brain. Acetylcholine synthesis is being studied by a new double label technique, using GLC-MS to measure the levels of acetylcholine. Cyclic nucleotides are being measured by radioimmunoassay. Rats are being made thiamine-deficient by feeding a diet deficient in thiamine and by treatment with the thiamine antagonists pyrithiamine and oxythiamine. They are being studied when they begin to lose weight and when they develop neurological abnormalities, and they are being sacrificed by focused microwave irradiation of the head. The degree of thiamine deficiency is being monitored by measuring the "TPP-effect" on blood transketolase. Controls include "reversed-deficiency" (i.e., thiamine-treated) animals as well as pair-fed and normal-fed controls. Morphological abnormalities associated with thiamine deficiency are also being monitored.